This proposal focuses on the development of a novel bifunctional drug screening assay for the discovery of specific inhibitors of human h-Ras protein utilizing the proprietary ATLAS (any target ligand affinity screen) approach, which was originally developed by th P.I., Dr. Pakula Ras is a member of a large family of related intracellular proteins, and is potentially an important therapeutic target for diseases associated with cellular proliferation. The approach depends initially on identifying auxiliary and inhibitory ligands for adjustment binding sites on Ras protein. The preparation of a bifunctional molecular comprised of the two small molecular ligands attached through a linker group will then be carried out. It is anticipated that the bifunctional molecule, obtained by tethering the two small ligands, will have a much higher affinity for the Ras protein.